This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Peripheral arterial disease (PAD) is characterized by lower limb arterial obstruction due to atherosclerosis that impairs blood flow to the lower limb. PAD is quite common with over 8 million affected individuals in the U.S. Over the past 6 years, our multi-disciplinary team of investigators has developed several new magnetic resonance measures to aid in the evaluation of PAD including atherosclerotic plaque volume measures in the superficial femoral artery, phosphocreatine (PCr) recovery kinetics after exercise by 31P spectroscopy (MRS), and first-pass contrast-enhanced calf muscle perfusion at peak exercise. The latter requires gadolinium chelates which are now contraindicated in advanced chronic kidney disease, whose risk factors overlap with PAD. Quantification of muscle blood flow and flow reserve without the use of contrast would thus be desirable in PAD patients with significant renal dysfunction. We hypothesize that both contrast and non-contrast flow reserve measures in PAD are feasible, perform better at 3T than 1.5T, and are reproducible. Thus, Specific Aim #1 is to develop and test MRI methods to quantify skeletal muscle blood flow and flow reserve at peak exercise in peripheral arterial disease, both with and without contrast (arterial spin labeling or ASL) in normal subjects and in PAD. We hypothesize that these novel methods will be be able to detect changes brought about by established therapies for PAD. Specific Aim #2 is to test the ability of peak exercise measures of calf muscle perfusion reserve and energetics to detect changes in PAD patients after percutaneous revascularization. Twenty five patients will be studied before, 4-8 weeks after, and 6 months after revascularization. Specific Aim #3 is to test the ability of peak exercise measures of calf muscle perfusion reserve and energetics to detect changes in PAD patients after supervised exercise therapy. Ninety five patients will be studied before and after a 12-week exercise program. All patients in Aims 2 and 3 will undergo first pass contrast-enhanced measures of perfusion reserve or ASL depending on underlying renal function, exercise 31P MRS measures of PCr recovery kinetics, as well as functional measures including treadmill exercise, VO2 testing, and 6-minute walk. Correlations will be examined between changes in calf muscle perfusion and energetics with improvements in functional capacity.